Objective: To study the associations between variants of mTORC1 of PI3K/AKT/mTOR pathway and colorectal cancer. Methods: In this hospital-based case-control study, at the First Affiliated Hospital, Xinjiang Medical University from 2000 to 2013, 665 primary colorectal cancer cases and 695 cancer-free controls were genotyped at 10 potentially functional single nucleotide polymorphism (SNPs) loci of mTORC1 (mTOR: rs1034528, rs2295080; Raptor: rs1062935, rs3751934; mLST8: rs3160, rs26865; DEPTOR: rs2271900, rs4871827; AKT1S1: rs2290774, rs2353005) to assess their associations with risk of colorectal cancer by Logistic regression analysis. Results: In single-locus analysis, found a significantly decreased risk of colorectal cancer associated with mLST8 rs26865 by recessive genetic model, especially in populations of ≤68 years of age (OR=0.64; 95%CI=0.43-0.96, P=0.031), female (OR=0.61; 95%CI=0.38-0.99, P=0.046), non-smoking (OR=0.55; 95%CI=0.35-0.87, P=0.010). mTOR rs1034528 CC genotypes were associated with higher risk of colorectal cancer in >68-year-old populations (OR=3.34; 95%CI=1.12-9.91, P=0.030). Raptor rs3751934 CA/AA genotypes were associated with lower colorectal cancer risk in population of body mass index(BMI)>25 kg/m(2) (OR=0.68; 95%CI=0.47-0.98, P=0.038); and AKT1S1 rs2290774 CC genotypes were associated with lower colorectal cancer risk in non-smoking population (OR=0.67; 95%CI=0.45-0.99, P=0.048). Furthermore, found that populations carrying more than two low-risk genotypes were associated with lower colorectal cancer risk, compared with that of populations carrying less than two low-risk genotypes (OR=0.74, 95%CI=0.58-0.95, P=0.017), especially in population of ≤68 years of age, male and BMI>25 kg/m(2,) and non-smoking. Conclusions: SNPs of mTORC1-related genes individually or jointly contribute to colorectal cancer susceptibility in Chinese. Further studies of larger cohorts are needed to validate the findings.
目的： 筛查及分析PI3K/AKT/mTOR信号转导通路中mTORC1基因多态性位点与结直肠癌发病风险的相关性及其临床意义。 方法： 收集2000年至2013年间新疆医科大学第一附属医院665例原发性结直肠癌患者和695名健康对照，通过病例－对照研究，运用Logistic回归分析mTORC1相关基因中10个多态位点(mTOR：rs1034528，rs2295080；Raptor：rs1062935，rs3751934；mLST8：rs3160，rs26865；DEPTOR：rs2271900，rs4871827；AKT1S1：rs2290774，rs2353005)与结直肠癌易感性的关系。 结果： mTORC1相关基因与结直肠癌发病风险相关，并与人群的年龄、性别、吸烟状态及体重指数相关。其中，mLST8 rs26865 AA基因型在≤68岁(OR＝0.64，95%CI＝0.43～0.96，P＝0.031)、女性(OR＝0.61，95%CI＝0.38～0.99，P＝0.046)、无吸烟人群(OR＝0.55，95%CI＝0.35～0.87，P＝0.010)中均能降低结直肠癌的发病风险；mTOR rs1034528 CC基因型在>68岁的人群中提高了结直肠癌的发病风险(OR＝3.34，95%CI＝1.12～9.91，P＝0.030)、Raptor rs3751934 CA/AA基因型在体重指数>25 kg/m(2)的人群中能降低结直肠癌的发病风险(OR＝0.68，95%CI＝0.47～0.98，P＝0.038)、AKT1S1 rs2290774 CC基因型在不吸烟的人群中能降低结直肠癌的发病风险(OR＝0.67，95%CI＝0.45～0.99，P＝0.048)。mTORC1低风险基因型叠加与结直肠癌发病风险相关性分析结果显示，同时携带两个以上低风险基因型的人群要比没有或只携带1个低风险基因型的人群患结直肠癌的风险要低(OR＝0.74，95%CI＝0.58～0.95，P＝0.017)，这在≤68岁、男性、体重指数>25 kg/m(2)及不吸烟人群中尤其明显。mLST8 rs26865基因型与mLST8及下游蛋白4EBP1和p70S6K的表达无相关性。 结论： mTORC1相关基因多态位点与中国新疆散发性结直肠癌的发生具有一定的相关性，但相关效应较低，尚需在大样本量的、多中心、不同种族的结直肠癌研究中加以验证。.
Keywords: Case-control studies; Colorectal neoplasms; Genetic predisposition to disease; mTORC1.